Prostate cancer, the most common non-skin cancer in N. America and Europe, forms in the tissues of the prostate (a gland in the male reproductive system found below the bladder and in front of the rectum). Prostate cancer affects one in six men, usually older men.
As men age, the prostate may get bigger and block the urethra or bladder. This may cause difficulty in urination or can interfere with sexual function. It is estimated that there are more than 2 million American men currently living with prostate cancer.
Older age, African American race and a family history of the disease can all increase the likelihood of a man being diagnosed with the disease. As men increase in age, their risk of developing prostate cancer increases exponentially. An estimated 230,000 new cases are diagnosed annually in the United States, with nearly 30,000 annual deaths.
African American men have higher incidence and at least double the mortality rates compared with men of other racial and ethnic groups. Historically, prostate cancer has been considered an older man`s disease, however the incidence is increasing in men in their 40s and 50s.
Prostate cancer usually grows slowly and initially remains confined to the prostate gland. While some types of prostate cancer grow slowly and may need minimal or no treatment, other types are aggressive and can spread quickly.
A diagnosis of prostate cancer can be scary not only because it can be life-threatening, but also because invasive treatments can cause side effects such as bladder control problems (incontinence) and erectile dysfunction (impotence). Men are classified as being at low, intermediate or high risk.
The criteria used to categorize the risk include the results of the prostate-specific antigen (PSA) blood test (which looks for a protein produced by the prostate gland and can help detect cancer), tumour aggressiveness and the clinical stage of the tumour.
Prostate Specific Antigen (PSA) is a protein produced by prostate cells which is often higher in the blood of men who have prostate cancer and is detected by performing a blood test. However, an elevated level of PSA does not necessarily mean you have cancer.
PSA test is used in conjunction with Digital Rectal Examination (DRE) of the prostate to help detect prostate cancer in men and for monitoring men with prostate cancer after treatment. However, much remains unknown about how to interpret the PSA test, its ability to discriminate between cancer and benign prostate conditions, and the best course of action if the PSA is high.
Because so many questions are unanswered, the relative magnitude of the test`s potential risks and benefits is unknown. When added to DRE screening, PSA enhances detection, but PSA tests are known to have relatively high false-positive rates, and they also may identify a greater number of medically insignificant tumours although we have to take in consideration the limitations of the standard biopsies.
The PSA test first became available in the 1980s, and its use led to an increase in the detection of prostate cancer between 1986 and 1991. In the mid-1990s, deaths from prostate cancer began to decrease, and some observers credit PSA testing for this trend. Others, however, point out that statistical trends do not necessarily prove a cause-and-effect relationship. The benefits of prostate cancer screening are still being studied. Two large international trials are looking into prostate cancer screening. In Europe the large ERSPC trial has stopped recruiting patients. In the USA the PLCO trial has closed and men taking part are now being followed up. Early results were released in March 2009.
The PCLO study compared 2 groups of men. One group had screening every year with the PSA test and rectal examination. The other group did not have screening as part of the study. The researchers found that screening did not reduce the number of deaths from prostate cancer after 11 years of follow up. The number of deaths was small in both groups. But the results are not clear, because some men in the trial group who were not supposed to have screening had PSA tests from their own doctors.
The ERSPC study is being carried out in 7 European countries. It compared men who had screening for prostate cancer with a PSA test every 4 years to men who had no screening. The early results show that PSA tests can detect very early prostate cancer and may reduce the number of deaths from the disease. But the men in the study need to be followed up for longer to be sure. So the men in the study will carry on being followed up over the next few years to see whether screening reduces the number who die due to prostate cancer. The combined final results of the PCLO and ERSPC trials are due in 2010.
Until a definitive answer is found, doctors and patients should weigh the benefits of PSA testing against the risks of follow-up diagnostic tests and cancer treatments. The procedures used to diagnose prostate cancer may cause mild side effects, including bleeding and infection. Treatment for prostate cancer often causes erectile dysfunction and may cause urinary incontinence.
PCA3 Score - What is PCA3?
Prostate Cancer gene 3 (PCA3) is a new Urinary derived gene test. PCA3 is highly specific to prostate cancer and this gene is upregulated by 66folds in tissue containing greater than 10% prostate cancer. This is in contrast to Prostate Specific Antigen (PSA), the blood test that is most commonly used to look for evidence of prostate cancer, which may be increased by conditions such as benign Prostatic enlargement (BPE) or inflammation of the prostate (prostatitis). The PCA3 test result is not affected by benign prostate conditions.
What does the test involve?
Prostate cells are shed into the urine following light prostatic massage or `attentive` digital rectal examination (DRE), similar to the examination normally performed by your doctor. Following the examination, you will be asked to pass urine and the first part of the voided urine specimen is collected and sent to the PCA3 laboratory for analysis.
Should I have my PCA3 tested?
If you are concerned about the possibility of prostate cancer because of an elevated PSA or are feeling insecure about a previously performed (negative) biopsy, the PCA3 urine test can provide additional information that may help you and your doctor to decide whether a (further) biopsy is really needed. As prostate cancer can also be found in patients whose PSA is normal, the PCA3 test may help give further reassurance that you do not have a prostate cancer despite a normal PSA level.
The PCA3 is not a "screening" test that can be performed in isolation to tell you whether or not you do have cancer. It should be seen as part of the number of tests in the assessment by your urologist and the results has to be taken into consideration along with the PSA level, DRE and any previous prostate biopsy.
As the PCA3 test is still a new test, we are still discovering the different ways in which it may help us investigate men who have concerns about prostate cancer. We will be happy to discuss whether PCA 3 testing is relevant to the assessment of your prostate and organize this investigation if necessary. Further Information is available at www.pca3.org.
Trans Rectal Ultrasound and Prostate Biopsy
If there is a suspicion of prostate cancer, your doctor may recommend a test with transrectal ultrasound. In this procedure, a probe inserted in the rectum directs sound waves at the prostate. The echo patterns of the sound waves form an image of the prostate gland on a display screen. This allows accurate measurement of the size of your prostate. To determine whether an abnormal-looking area is indeed a tumour, the doctor can use the probe and the ultrasound images to guide a biopsy needle to the suspected tumour area under local anaesthetic. The needle collects a few pieces of prostate tissue for examination with a microscope.
There is a small risk of infection related to this procedure, therefore you will be commenced on antibiotics the day prior to the biopsy and will be advised to complete the course of antibiotics. There is also a small risk of seeing blood in the urine, semen and in the back passage, although these are transient and often resolve within two weeks post biopsy. It is important that you drink a lot of water to flush out the small amount of blood from the prostate and guard against infection. The results of a biopsy are available within days.
What if the biopsy shows no prostate cancer?
Unfortunately, a negative biopsy does not give a guarantee that no cancer is present due to sampling error (like looking for a needle in a haystack). Your urologist will want to follow you up with a repeat PSA and perhaps PCA3 test after 6-12 months. Further prostate biopsy might be necessary especially if you have family history of prostate cancer, or other parameters seen in the biopsy tissue.
It is important to reduce your risk of prostate cancer by making any necessary lifestyle and dietary changes
Diet and supplements to reduce the risk of Prostate Cancer
”You are what you eat” (Ayurveda, 700 B.C.)
In recent years there has been an increasing realization that what we put into our bodies has the potential to significantly affect its metabolism and the way the body reacts to environmental influences such as carcinogens, for example. Twin and migration studies have demonstrated that 20% of cases prostate cancers are genetic, which means that 80% are environmental, the strongest influence suspected being diet.
The following have been shown in medical studies to:
Reduce the risk of prostate cancer
- Vitamins A, D and E
- Selenium - found in Brazil nuts
- Carotenoids - especially lycopene, found in (particularly cooked) tomatoes
- Phytoestrogens - especially soy products, as well as cereals, fruit and vegetables
- Chinese green tea
Increase the risk of prostate cancer
- A diet which is heavy in animal fat (red meat and dairy products)
Although a balanced diet is part of healthy living, our lifestyle often makes this goal difficult to achieve. A number of plant extracts and minerals have historically been used over the centuries for specific medical conditions, some of which have now been used to make drugs (e.g. aspirin and digoxin) and have a scientific basis for their use (e.g. selenium, zinc, saw palmetto). The use of supplements and herbs is not guaranteed to cure any condition but offers an alternative and natural pathway to explore which is at very worst unlikely to do harm and at best might make a positive and significant difference to symptoms and the condition causing it. As always, do not exceed the specified dosage as this might be harmful.
How do I work out how serious my Prostate cancer is?
The underlying risk of the cancer is determined principally by:
PSA: the higher the PSA, the more likely the cancer is outside the prostate, the faster the rate of change, the more likely serious cancer is present.
Gleason Score: this is a measure of how aggressive the cancer is. The two commonest patterns of cancer are each graded from 1 to 5. The two grades are summed and the total is known as the Gleason score. Therefore, this ranges from 2 to 10. Most cancers have a Gleason Score of 6: the most serious is 10 and the best is 2.
Cancer Stage: This refers to how far the cancer has spread and can be determined partially by prostate examination with a finger, and sometimes with transrectal ultrasound at the time of prostate biopsies, a Bone scan or Magnetic Resonance Imaging (MRI) scan. Bone scans indicate whether there is cancer in the bones. Sometimes, the lymph nodes in the pelvis are sampled laparoscopically to determine if cancer is present there.
Prostate Cancer Treatments Options
Prostate cancer treatment ranges from minimally-invasive (brachytherapy, cryotherapy) to major surgery (radical prostatectomy.)
In some cases, "watchful waiting" (keeping the cancer under close observation for signs of progression) may be an option.
The "Best" Prostate Cancer Treatment
The best prostate cancer treatment depends upon a man`s age and general health, the stage of his prostate cancer and his personal decision.
Watchful Waiting / Active Surveillance
A man who has selected watchful waiting is a man who has chosen not to have immediate prostate cancer treatment. During the watchful waiting period, the physician keeps the cancer under close watch and this is why it sometimes is referred to as active surveillance.
The logic for watchful waiting is simple: prostate cancer often develops very slowly. With watchful waiting, the patient takes the time to consider possible treatment options. In some cases particularly with older men the prostate cancer patient will die of other causes rather than from prostate cancer.
Other factors that motivate men to choose watchful waiting are the intrusiveness of many available treatments, the potential side effects, and in some cases limited long-term data.
Watchful waiting entails regular PSA tests, digital rectal exams and/or other tests. "Waiting" means being alert for any indication that the cancer has developed to the point that it may require surgery or other treatment. Prostate biopsy will be repeated after a few months.
Choosing "Watchful Waiting"
Generally, watchful waiting is appropriate for men who meet one or more of these criteria:
- Short life expectancy
- Have significant other illnesses
- Have small tumours, a low Gleason score, and a low PSA level
- Any man fearful of treatment, regardless of age or health, also may choose watchful waiting.
Risks of Watchful Waiting
The major risk of watchful waiting is that without treatment, prostate cancer can grow and spread outside the prostate capsule before your next doctor`s visit
3DPM and Focal Therapy
This is analyzed in the sections of News/Focal Therapy and Cryotherapy.
Brachytherapy is a minimally invasive procedure where the doctor implants tiny permanent radioactive seeds (about the size of a grain of rice) into the prostate. They irradiate the cancer from inside the gland. The implanted seeds are small enough that they will not be felt by the patient. Depending on your circumstances, either radioactive Iodine (I -125) or palladium (Pd-103) will be used. Brachytherapy is also referred to as interstitial radiation therapy or seed implant therapy.
Before the seeds are implanted under anaesthesia, needles containing the seeds are then inserted through the skin of the perineum (the area between the scrotum and anus) using ultrasound guidance. The seeds remain in the prostate, where the radioactive material gives off localized radiation for a number of months to destroy the prostate cancer.
Seed implantation is an effective treatment for men with localized prostate cancer. Seed implantation requires no surgical incision and offers men a short recovery time.
External Beam Radiation Therapy (EBRT)
External beam radiation therapy (EBRT) treats prostate cancer with radiation. Before treatment starts, the doctor will order a scan or other tests to check the location and possible extension of the cancer.
During the treatment, a machine targets a beam of ionizing irradiation at the target tissue. The treatment damages genetic material in all dividing cells within the target lesion. This prevents the cells from growing and they eventually die.
undergoing EBRT generally receive treatment at an outpatient center five days a week for six to eight consecutive weeks.
When is EBRT Used?
EBRT is an option when the cancer is confined or slightly outside the prostate gland, it may be used alone or combined with medications or surgery.
All prostate cells are stimulated by the male hormone testosterone. The testicles produce 95% of a man`s testosterone. The job of testosterone is to regulate the normal function, growth and development of the male reproduction organs, including the prostate gland. However when prostate cancer develops, testosterone can make the cancer grow much faster.
By either removing the testicles, or by interfering with the action of testosterone in different ways, the cancer is starved and it shrinks.
There are different ways to do this:
- Surgical castration is an operation to remove the testicles (or remove just the parts of the testicles which produce testosterone). The procedure is called subcapsular orchidectomy.
- Luteinizing hormone-releasing hormone (LHRH) agonist injections stop the testicles making testosterone. This drug is usually given by injection once a month or every three months. The therapy spares the testicles and works just as well as surgical castration.
- Anti-androgen tablets block the effect of testosterone in the body.
- Maximum androgen blockade (MAB), sometimes tablets and injections are used together.
When is Hormone Therapy Used?
If the cancer has spread outside the prostate gland to other parts of the body, physicians normally use hormonal deprivation therapy to slow the spread or growth of the cancer.
Hormone therapy may also be used to shrink the size of the prostate gland before you receive another kind of treatment (such as radiotherapy or brachytherapy).
Men whose cancer has returned after radical prostatectomy or radiation therapy may be offered hormonal therapy
Risks and Side Effects of Hormonal Therapy
All forms of hormone therapy have roughly similar side effects but every man reacts in a different way - some get a lot of side effects, some get very few.
All types of hormonal therapy may cause side effects generally known as the "Male Hormonal Withdrawal Syndrome." This syndrome may include symptoms like:
- Loss of sexual desire
- Hot flashes
- Weight gain
- Loss of muscle mass
Other Potential Problems:
Surgical castration is not reversible. In some cases it may require a stay in hospital.
LHRH agonists may tend to increase tumour growth at first and make the patient`s symptoms worse. This problem is called "tumour flare."
Androgen blockade treatment may cause patients to have nausea, vomiting or tenderness and swelling of their breast tissue.
Radical prostatectomy is major surgery performed under general anaesthesia that removes the entire prostate gland plus some surrounding tissue. During the procedure the pelvic lymph nodes may also be sampled for a biopsy. The goal is to remove the cancer entirely and prevent its spread to other parts of the body.
Facing any kind of urologic surgery creates a great deal of anxiety for most men. Among your concerns is: "Will my body function normally following surgery?" Traditional open urologic surgery - in which large incisions are made to access the pelvic organs - has been the standard approach when surgery is warranted. Yet common drawbacks of this procedure include significant post-surgical pain, a lengthy recovery and an unpredictable, potentially long-term impact on continence and sexual function.
Fortunately, less invasive surgical options are available to many patients facing surgery for prostate cancer. The most common of these is Laparoscopic Prostatectomy, which uses small incisions. While laparoscopy can be very effective for many routine procedures, limitations of this technology prevent its use for more complex urologic surgeries.
A new category of surgery, introduced with the development of the da Vinci® Surgical System, is being used by an increasing number of surgeons worldwide for Robotic Prostatectomy.
How do I decide what to do?
First of all, it has to be clear the stage and the grade of the disease so, that you could have the scientifically beneficial options for you.
Ask for hand-outs of the various nomograms regarding success, survival, possibility of adjuvant therapy, etc.
You have to trade-off the advantages over the disadvantages of each option. It depends on the relative values of each. This is best done by discussing the issues with a doctor and close family. In general, if the thought of having cancer and not doing the most possible to get rid of it dominates your thinking, then you should choose an interventional treatment. There is no caste iron evidence to indicate one treatment is better than another, but many doctors believe that radical prostatectomy offers the best chance of prolonging life. It becomes more important to maximally remove the cancer if it is high risk or there are many years of life possibly ahead. On the other hand, active monitoring may be the best option if quality of life is more important than preserving a few years of life especially if there is uncertainty over the benefit of treatment and the cancer does not seem obviously to be high risk. A second opinion is often helpful.
Several websites offer details and on-line help in making decisions including
Frequently asked questions
Who is a candidate for surgery?
Any patient who wants the most traditional, most reliable form of treatment. Young patients and those with aggressive disease frequently choose surgery because of the risks of developing secondary cancers with radiation treatment and the larger possibility of back-up or "salvage" treatments if cancer recurs after surgery.
Where is the procedure being performed?
This procedure is being performed to a few private hospitals where I work.
What is "robotically assisted prostatectomy?"
A few years ago the technique of removing the prostate using small instruments through small incisions was described for the prostate. However, due to the position of the prostate and its proximity to many vital structures, laparoscopic prostatectomy is very technically challenging but this was easily overwhelmed with structured training during the last decade. In the Center of Avant-garde Minimally Invasive Urology we offer robotically assisted laparoscopic radical prostatectomy with the Freehand® of Prosurgics™ (http://www.freehandsurgeon.com/) that enables detailed rock-stable vision which is vital for the recognition of fine anatomical structures. The surgical robot (DaVinci) helps make laparoscopic prostatectomy easier for those that lack of laparoscopic training by having joints and digits that rotate in more diverse directions that human fingers and wrists. In robotically assisted prostatectomy, the surgeon sits next to the patient
How long will I be in the hospital?
Most patients who have their prostates removed are in the hospital one to two nights after surgery. The aouthor at the AvantGrade Center use special "pain buster" devices. These devices slowly release numbing medication around the wound so the pain is kept to a minimum during recovery. Insurance companies generally pay for 2-3 nights in the hospital after surgery, so if you are coming from a long ways away or if you are still having pain, then the option is open to stay longer.
How long will it take to recover?
After discharge from the hospital, patients generally have a foley catheter (hollow tube) in their urethra (tube carrying urine in the center of the penis). That catheter is left in place for 10-14 days. Once the catheter is removed, men do experience difficulty with continence, or urinary control. This is because the prostate usually holds in all of the urine without a man having to think about urinary control. However, there is a muscle located beyond the prostate that eventually learns to take over control of the urinary stream. It takes, on average, 6 weeks for this weaker, smaller muscle to be trained to provide good urinary control. Most men start with "Depends" undergarments since the amount of leakage can be generous during the first week. By the second week after removal of the catheter, most men do well with thick sanitary pads. By 6 weeks after catheter removal men are wearing 1-2 thin sanitary pads as a back up, or none at all. Because of the issues with the catheter and urinary control, most men take 3-6 weeks off for surgery.
What are my limitations after surgery?
We recommend that men who have undergone surgery refrain from driving for 2 weeks after surgery, while the Foley catheter is in. Once the catheter has been removed, and once a man is no longer requiring narcotic pain medication, he can drive again. We also recommend that men refrain from lifting anything heavier than ten pounds or performing activities that would put a lot of pressure on the area of their previous prostate (horseback riding or biking) for six weeks.
Where is my incision located?
The traditional incision is approximately 4 inches long and is located from the pubic bone up towards the belly button. The laparoscopic main incision is less than 1.5 inches and the others of 0.5cm each.
Is there anything I can do to prepare for my surgery?
Studies have shown that men who perform Kegel exercises (squeezing of the muscle that will be used to hold the urine in after the prostate is removed) have better control of their urine sooner. Additionally, studies have shown that men who smoke have fewer complications if they give up cigarettes at least 2 weeks prior to their surgery. Some studies have shown that diets low in saturated fats may help prevent prostate cancer. The effect of a low-fat diet on prostate cancer after it has been diagnosed is unknown.
Is there anything I can do to prevent getting prostate cancer in the future?
Again, studies are unclear on the benefit of intervention with diet after prostate cancer is diagnosed. Some studies indicate that selenium, vitamin E, and lycopene may be helpful in preventing prostate cancer in the first place, so it these elements may be useful in preventing recurrence. One should not take more than the recommended daily allowance to prevent toxicities (such as a stroke) with high doses of these supplements. A diet low in saturated fats and a lifestyle incorporating 30 minutes of exercise 3 times per week is recommended to keep all cancers to a minimum.
What are the chances my cancer would re-occur after surgery?
There are many sophisticated tables predicting one’s chance of cure with surgery. In general, the higher one’s PSA and the higher one’s Gleason score at the time of surgery, the more likely prostate cancer will return. Your doctor can help inform you if your cancer is considered low, intermediate, or high risk based on the factors outlined above. In general, men with low-risk prostate cancer have a 5-10% risk of cancer recurrence over time. Men with intermediate risk prostate cancer have a 15-20% risk of cancer recurrence, and men with high-risk prostate cancer have a 50% risk of cancer recurrence. Additionally, when cancer is found at the edge of the prostate when it is removed, there is a 40-50% chance cancer will still be present and will need further treatment. All men with prostate cancer who are treated by surgery should have a PSA test (blood work) drawn every six months for the rest of their lives.
What is Gleason grade?
Dr. Gleason is a pathologist and he noted that the more scattered prostate cancer cells look under the microscope, the more aggressive the prostate cancer. The Gleason sum or grade is made up of two individual numbers that reflect the most common patterns of a prostate cancer when it is viewed under a microscope. In general, a Gleason sum of 6 or less is considered low grade or slow growing, a Gleason sum of 7 is considered intermediate risk or moderately aggressive growth, and a Gleason sum of 8-10 is considered high grade or aggressive.
How will I know if my prostate cancer has come back?
Following surgery, a man’s PSA should be zero. The most sensitive most laboratories can report is <,,,0.1. As long as one’s PSA is <,,,0.1 there is no prostate cancer or tissue remaining. However, if the PSA is greater than 0.1 after surgery, there is a chance the prostate cancer has recurred and the patient should be seen by his urologist as soon as possible.
Where does prostate cancer re-occur?
Prostate cancer is a very unusual cancer because it grows slowly in most cases. This means it can re-occur even 15-20 years after treatment. This fact highlights the importance of semi-annual blood tests for PSA following prostatectomy. In general, cancer that re-occurs within 2 years is found distantly, in the bones or liver, whereas cancer that re-occurs later is found in the area of the previous prostate.
What options are available when prostate cancer re-occurs?
When prostate cancer re-occurs in the bones or liver (cancer outside the prostate is considered metastatic), the cancer is no longer curable. Radiation can be given to the bones to decrease pain and surgery can be performed to stabilize joints can decrease the risk of bone fractures, but this does not add to survival length. Medication to decrease testosterone is generally given in patients with metastatic disease, which drives PSA down temporarily, but is not curative. On the other hand, if there is no evidence of cancer outside the previous site of the prostate but the PSA has risen after surgery, radiation can be given to this site and can be curative in 50% of patients.
What are the side effects of prostatectomy?
99% of patients obtain urinary control after the procedure. Many patients experience short-term incontinence following prostatectomy. The muscles that normally control retention of urine in the bladder are removed during the surgery and it takes several weeks for other muscle groups to gain strength and take over this function. There is a temporary time period where a man has to strengthen a muscle he is not used to using to regain urinary control. Since the newly trained muscle is never as strong as the original muscles in the prostate about 10% of men leak a drop or two of urine if they lift something heavy or cough or sneeze. Most men feel like continence is not a problem after surgery in my hands, beginning about 3-4 weeks after the procedure. Another common side effect is erectile dysfunction, or "ED". Varying degrees of ED may occur in 40-50% of patients who undergo radical prostatectomy. The younger a patient is before surgery and the better his erectile function, the more likely he will maintain his erectile function after surgery.
What are the treatments for E.D. (erectile dysfunction) after surgery?
Patients are offered a variety of options to get them back to potency levels close to what they were prior to surgery. The list includes oral agents such as Viagra®, Lavitra®, and Cialis®, injectable agents such as Caverject®, a vacuum erection device (used externally), and if all of these are ineffective, a surgical implant. Treatments for E.D. are generally started 6 weeks following the procedure and function usually improves slowly for up to one year following the procedure. It is important to realize that the nerves that produce orgasm or climax are not damaged during the procedure. Men can still climax, even without erection. Additionally, it is important to know that during climax or orgasm, no fluid will come from the penis after prostatectomy since the prostate is what provides the majority of the fluid during ejaculation.
Will I have a lot of bleeding with the procedure?
About 10% of patients require blood transfusion with the procedure, as the prostate is a very vascular organ. A minimum of cauterization should be performed with prostatectomy to maximize the chance of return of potency. Most men choose to donate 2 units of blood in case they should need transfusion during the surgery. Their donated blood is given back to them during surgery to help them feel stronger in recovering.
What should I watch out for after surgery?
The most important thing to watch for following surgery is a painful, swollen, or red calf. This, particularly if located on only one side, can be the sign of a blood clot. Blood clots are more common following surgery and are more common in patients who have had cancer. This blood clot can move to the lung which is very dangerous, so any patient with the symptoms of a painful, swollen, or red calf should seek treatment in the closest emergency room as soon as possible.